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Details

Stereochemistry RACEMIC
Molecular Formula C18H23NO.ClH
Molecular Weight 305.842
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ORPHENADRINE HYDROCHLORIDE

SMILES

Cl.CN(C)CCOC(C1=CC=CC=C1)C2=C(C)C=CC=C2

InChI

InChIKey=UQZKYYIKWZOKKD-UHFFFAOYSA-N
InChI=1S/C18H23NO.ClH/c1-15-9-7-8-12-17(15)18(20-14-13-19(2)3)16-10-5-4-6-11-16;/h4-12,18H,13-14H2,1-3H3;1H

HIDE SMILES / InChI

Molecular Formula C18H23NO
Molecular Weight 269.3813
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB01173 | https://www.drugs.com/cdi/orphenadrine.html

Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class used to treat muscle pain and to help with motor control in Parkinson's disease but has largely been superseded by newer drugs. Orphenadrine binds and inhibits both histamine H1 receptors and NMDA receptors. It restores the motor disturbances induced by neuroleptics, in particular, the hyperkinesia. The dopamine deficiency in the striatum increases the stimulating effects of the cholinergic system. This stimulation is counteracted by the anticholinergic effect of orphenadrine. It may have a relaxing effect on skeletal muscle spasms and it has a mood elevating effect. Orphenadrine is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Orphenadrine is an anticholinergic with a predominantly central effect and only a weak peripheral effect. In addition, it has mild antihistaminic and local anesthetic properties. Parkinson's syndrome is the consequence of a disturbed balance between cholinergic and dopaminergic neurotransmission in the basal ganglia caused by a decrease in dopamine. Orphenadrine restores the physiological equilibrium and has a favorable effect on the rigidity and tremor of Parkinson's disease and Parkinsonian syndromes. Adverse reactions of orphenadrine citrate are mainly due to the mild anticholinergic action of orphenadrine citrate and are usually associated with higher dosage. Dryness of the mouth is usually the first adverse effect to appear. When the daily dose is increased, possible adverse effects include tachycardia, palpitation, urinary hesitancy or retention, blurred vision, dilatation of pupils, increased ocular tension, weakness, nausea, vomiting, headache, dizziness, constipation, drowsiness, hypersensitivity reactions, pruritus, hallucinations, agitation, tremor, gastric irritation and rarely urticaria and other dermatoses

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
97.7 µM [IC50]
6.0 µM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
DISIPAL

Approved Use

Orphenadrine citrate extended-release tablets are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions.

Launch Date

1957
Primary
DISIPAL

Approved Use

Orphenadrine citrate extended-release tablets are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions.

Launch Date

1957
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
41.89 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
49.19 ng/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1739.15 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1772.44 ng × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
21.02 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
22.29 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORPHENADRINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
7%
ORPHENADRINE plasma
Homo sapiens
Doses

Doses

DosePopulationAdverse events​
500 mg 1 times / day steady, oral
Highest studied dose
Dose: 500 mg, 1 times / day
Route: oral
Route: steady
Dose: 500 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: depression
Age Group: adult
Sources:
2 g single, intramuscular
Overdose
unhealthy, adult
Other AEs: Toxic reaction (NOS)...
2 g single, intravenous
Overdose
unhealthy, adult
Other AEs: Toxic reaction (NOS)...
2 g single, oral
Overdose
unhealthy, adult
Other AEs: Toxic reaction (NOS)...
AEs
PubMed

PubMed

TitleDatePubMed
Prochlorperazine in childhood: side-effects.
1977
Reversal of orphenadrine-induced ventricular tachycardia with physostigmine.
1991 Nov-Dec
[Diagnostic image (17). Acute dystonia induced by prochlorperazine].
2000 Dec 23
[Experience gained with the drug amizon in the treatment of patients with mumps, with special reference to its effects on some biochemical markers].
2001 Mar-Apr
Therapeutic response of benzodiazepine, orphenadrine citrate and occlusal splint association in TMD pain.
2003 Apr
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.
2003 Jan 1
Neuronal sensitization and its behavioral correlates in a rat model of neuropathy are prevented by a cyclic analog of orphenadrine.
2003 Jun
Cytochrome P-4503A1 catalyzes the formation of MA1 from territrem a in liver microsomes of 7-week-old female Wistar rats.
2003 Mar 14
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia.
2003 Nov 17
Drug-drug interactions of Z-338, a novel gastroprokinetic agent, with terfenadine, comparison with cisapride, and involvement of UGT1A9 and 1A8 in the human metabolism of Z-338.
2004 Aug 23
Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer.
2004 Jan 12
Objective high-frequency tinnitus of middle-ear myoclonus.
2004 Mar
Alternatives to levodopa in the initial treatment of early Parkinson's disease.
2005
Comparison of the analgesic effects of a fixed-dose combination of orphenadrine and diclofenac (Neodolpasse) with its single active ingredients diclofenac and orphenadrine: a placebo-controlled study using laser-induced somatosensory-evoked potentials from capsaicin-induced hyperalgesic human skin.
2005
Restless legs syndrome: diagnosis and review of management options.
2006 Jun
A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer.
2006 May 24
Epirubicin/paclitaxel/etoposide in extensive-stage small-cell lung cancer: a phase I-II study.
2006 May 8
Acute adverse cutaneous reaction after the concomitant use of venlafaxine and orphenadrine citrate plus paracetamol in a depressed patient.
2006 Sep
Evaluation of enantioselective binding of basic drugs to plasma by ACE.
2007 Aug
[Enzyme kinetics of schizandrin metabolism and sex differences in rat liver microsomes].
2007 Jul
Effect of warnings in a medical journal on the use of orphenadrine.
2008 Aug
Pharmacologic profiling of human and rat cytochrome P450 1A1 and 1A2 induction and competition.
2008 Dec
Are there alternatives to the use of quinine to treat nocturnal leg cramps?
2008 Feb
Genetic and chemical modifiers of a CUG toxicity model in Drosophila.
2008 Feb 13
Effects of CYP inducers and inhibitors on the pharmacokinetics of intravenous theophylline in rats: involvement of CYP1A1/2 in the formation of 1,3-DMU.
2008 Jan
Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells.
2008 May
Demographics of toxic exposures presenting to three public hospital emergency departments in Singapore 2001-2003.
2009 Apr
Evaluation of luciferin-isopropyl acetal as a CYP3A4 substrate for human hepatocytes: effects of organic solvents, cytochrome P450 (P450) inhibitors, and P450 inducers.
2009 Aug
Effects of cytochrome P450 inducers and inhibitors on the pharmacokinetics of intravenous furosemide in rats: involvement of CYP2C11, 2E1, 3A1 and 3A2 in furosemide metabolism.
2009 Jan
Drugs associated with more suicidal ideations are also associated with more suicide attempts.
2009 Oct 2
Orphenadrinium picrate picric acid.
2010 Feb 24
(2-Methyl-phen-yl)(phen-yl)methanol.
2010 Jul 31
Opiate sparing effect of fixed combination of diclophenac and orphenadrine after unilateral total hip arthroplasty: A double-blind, randomized, placebo-controlled, multi-centre clinical trial.
2010 Nov
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Patents

Patents

Sample Use Guides

Acute musculoskeletal conditions: 100 mg orally twice a day (morning and evening) or 60 mg by intramuscular or intravenous injection. May repeat every 12 hours. Quinine-resistant leg cramps: 100 mg orally at bedtime.
Route of Administration: Other
In Vitro Use Guide
An aliquot (400 mkl) of the brain membrane suspension (0.14 mg of protein), 100 mkl of (-)3H-QNB (0.95 nM) (specific activity 46 Ci/mmol), and 50 mk1 of the competing drugs at various concentrations were preincubated for 10 min. and thereafter incubated for 60 min. at 25C in 50 mM Tris-HC1 buffer (PH 7.4). When binding to heart and lung membranes was studied, 500 nkl of homogenate (protein contents were 0.58 mg and 0.54 mg of rat heart and lung tissue and 0.63 mg of guinea pig lung tissue was added to tubes containing 500 mkl of 50 mM Tris-HC1 buffer (PH 7.4), 100 mk1 of (-)3H-QNB (final concentration 0.4 nM) and 100 mkl of buffer (total binding) or unlabeled Orphenadrine.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:26:14 GMT 2023
Edited
by admin
on Fri Dec 15 16:26:14 GMT 2023
Record UNII
UBY910DUXH
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ORPHENADRINE HYDROCHLORIDE
EP   MART.   ORANGE BOOK   VANDF   WHO-DD  
Common Name English
ORPHENADRINE HYDROCHLORIDE [EP IMPURITY]
Common Name English
Orphenadrine hydrochloride [WHO-DD]
Common Name English
ORPHENADRINE (CHLORIDE)
Common Name English
ORPHENADRINE HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
ORPHENADRINE HYDROCHLORIDE [MART.]
Common Name English
MEPHENAMIN
Brand Name English
NSC-82357
Code English
ORPHENADRINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
ORPHENADRINE HYDROCHLORIDE [VANDF]
Common Name English
DISIPAL
Brand Name English
ORPHENADRINE HCL
Common Name English
Classification Tree Code System Code
WHO-VATC QN04AB02
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
WHO-ATC N04AB02
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
NCI_THESAURUS C29704
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C78075
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
PRIMARY
RXCUI
202723
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
PRIMARY RxNorm
EPA CompTox
DTXSID5025815
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
PRIMARY
NSC
82357
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
PRIMARY
FDA UNII
UBY910DUXH
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
PRIMARY
DRUG BANK
DBSALT001021
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
PRIMARY
PUBCHEM
9568
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
PRIMARY
CHEBI
60902
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
PRIMARY
CAS
341-69-5
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
PRIMARY
SMS_ID
100000085503
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
PRIMARY
EVMPD
SUB03547MIG
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
PRIMARY
ECHA (EC/EINECS)
206-435-4
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
PRIMARY
ChEMBL
CHEMBL900
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
PRIMARY
WIKIPEDIA
Orphenadrine hydrochloride
Created by admin on Fri Dec 15 16:26:14 GMT 2023 , Edited by admin on Fri Dec 15 16:26:14 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY